Issn Print: 0955-8810
Publication Date: 2000/06/01
DEVELOPMENTAL RELATED CHANGES OF NEUROTROPHIC FACTOR EXPRESSION IN ANIMAL MODELS OF SCHIZOPHRENIA
M.A. Riva; M. Roceri; R. Molteni; B. Ellenbroek; G. Racagni
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Author Information: Institute of Pharmacological Sciences, University of Milan, Italy
Excerpt
It is well accepted that events that interfere with the normal program of neuronal differentiation and brain maturation may be relevant for the etiology of schizophrenia, setting the stage for synaptic disorganization that becomes functional late in adolescence. In order to investigate molecular determinants for these events, we examined the modulation of the neurotrophic factors FGF-2 and BDNF in putative neurodevelopmental models for schizophrenia. These neurotrophic molecules are known to have a role in brain maturation, and they are important players in neuronal plasticity. The goal of this study was to determine their contribution in long term changes in brain function following stress events during development. Specifically we investigated the effect of a prenatal exposure to corticosterone as well as the impact of 24 h maternal separation at postnatal day 9 (experiments were carried out in accordance to 86/609/EEC). Under both experimental conditions, we found that in adulthood the expression of BDNF and FGF-2 was reduced in the hippocampus, an effect that might render some cells more vulnerable to challenging events. Furthermore we found that in these animals the acute modulation of neurotrophic factor in response to stress was altered, indicating a persistent functional impairment in the regulation of these trophic molecules. We propose that events taking place during brain maturation can modulate the expression of neurotrophic factors within selected brain regions thus contributing to permanent structural and functional alterations leading to an increased vulnerability for psychiatric diseases.
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